25.3.1.3 Thrombolytics

The last group of antithrombosis drugs are the thrombolytics (fibrinolytics). These drugs are used to dissolve clots that have already formed. They are usually administered intravenously to clear a blocked blood vessel (for example in coronary thrombosis) and work by promoting the conversion of plasminogen to plasmin, a serine protease enzyme that hydrolyses fibrin, dissolving the clot, allowing reperfusion to occur.

The first drug in this class to be used was streptokinase, a protein isolated from beta-haemolytic Streptococci. Streptokinase activates plasminogen and promotes its conversion to plasmin. However, streptokinase causes a systemic fibrinolytic effect that can lead to bleeding problems and this agent has been replaced by tissue-type plasminogen activators (tPAs) such as alteplase, tenecteplase and reteplase. These agents have been produced by recombinant DNA technology and work locally on the thrombotic fibrin to produce fibrinolysis. Bleeding complications including gastrointestinal haemorrhage and stroke have been shown to occur with their use.